Retina as a window to systemic hypertension: From hypertensive retinopathy to artificial intelligence-driven microvascular biomarkers

Table 1 Landmark epidemiological studies of quantitative retinal vascular parameters and cardiovascular outcomes

Ref.	Cohort	Design and sample	Retinal parameter	Outcome	Principal finding
Sharrett et al[19], 1999	ARIC	Population-based cross-sectional, middle-aged adults	CRAE	Blood pressure	Mean arterial pressure was the dominant systemic determinant of narrower CRAE
Wong et al[54], 2004	ARIC	Prospective cohort	AVR	Incident hypertension	Smaller AVR predicted incident hypertension over 3 years
Ding et al[20], 2014	IPD meta-analysis, 6 cohorts	Individual-participant meta-analysis	CRAE, CRVE	Incident hypertension	Narrower arterioles and wider venules independently predicted incident hypertension
Kawasaki et al[21], 2009	MESA	Multi-ethnic prospective cohort	CRAE	Incident hypertension	OR = 1.34 (95%CI: 1.18-1.52) per 1-SD decrease in CRAE
Smith et al[22], 2004	Blue Mountains Eye Study	Population-based prospective cohort	Arteriolar calibre	5-year incident severe hypertension	Arteriolar narrowing predicted incident severe hypertension
Wong et al[23], 2002	ARIC	Prospective cohort	AVR	Incident coronary heart disease	Association present in women, absent in men
Seidelmann et al[24], 2016	ARIC	Long-term prospective cohort	CRAE, CRVE	Stroke, heart failure, mortality	Vessel calibres predicted long-term ischaemic stroke, heart failure and all-cause mortality
McGeechan et al[25], 2009	IPD meta-analysis	20798 participants, 945 stroke events	CRVE, CRAE	Incident stroke	CRVE: HR = 1.15 (95%CI: 1.05-1.25) per 20 μm; CRAE: HR = 1.00 (95%CI: 0.92-1.08)
McGeechan et al[26], 2009	IPD meta-analysis	Pooled cohorts	CRAE, CRVE	Coronary heart disease	HR = approximately 1.16-1.17 per 20 µm in women; no association in men
Liew et al[29], 2021	-	Population-based	Fractal dimension	Stroke mortality	Stroke mortality 7.7% in lowest vs 1.3% in highest fractal-dimension quartile
Triantafyllou et al[55], 2013	-	Cross-sectional, ABPM sub-phenotypes	AVR	Hypertension phenotype	AVR 0.820 normotension, 0.739 white-coat, 0.736 sustained, 0.716 masked hypertension

ARIC: Atherosclerosis Risk in Communities; MESA: Multi-ethnic study of atherosclerosis; CRAE: Central retinal arteriolar equivalent; CRVE: Central retinal venular equivalent; AVR: Arteriolar-to-venular ratio; IPD: Individual participant data; ABPM: Ambulatory blood pressure monitoring.